Study of immunoglobulins in various body fluids, especially in serum, urine and cerebrospinal fluid (CSF), is important for understanding the pathomechanism of a variety of diseases and for diagnosing and monitoring diseases. Protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) are key techniques to identifiy protein abnormalities and to detect abnormal immunoglobulins (paraproteins) in body fluids. The paraproteins are the products of clonal or oligoclonal proliferation of plasma cells and, as such, may represent full immunoglobulins, free heavy chains, and/or free light chains of immunoglobulins. Correct identification of paraproteins can be hampered, however, by the occurrence of pseudoparaproteins (P-proteins). P-proteins are normally occurring proteins that mimic M-proteins in protein electrophoretic patterns. Over the past few months, we have observed several cases of urine P-proteins that had not been described in the existing literature. Using a combination of various analytical techniques (e.g., electrophoresis in agarose and polyacrylamide gel, immunoelectrophoresis, and mass spectrometry), we are now in the process to fully identify these P-proteins.[unreadable] In a collaborative study, we investigated possible associations between silicone breast implants and the occurrence of serum paraproteins as indicators of benign or malignant lymphoproliferative disorders, and, in particular, benign monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Prior studies have suggested abnormalities of serum proteins, including paraproteins, in women with silicone implants but did not control for the presence of connective-tissue disease (CTD). In our retrospective case-control study, performed in tertiary-care academic centers, we assessed possible alterations of serum proteins, including paraproteins, in such a population. Seventy-four women with silicone implants who subsequently developed CTD and 74 age- and CTD-matched women without silicone implants were assessed in the primary study; other groups were used for additional comparisons. Routine serum protein determinations and high-sensitivity protein electrophoresis and immunofixation electrophoresis were performed for detection of paraproteins. Women with silicone implants, either with or without CTD, had significantly lower serum total protein and alpha-1, alpha-2, beta, and gamma globulins, and IgG levels compared to those without silicone implants. There was no significant difference, however, in the frequency of paraproteinemia between women with silicone implants and CTD (9.5%) and age- and CTD-matched women without silicone implants (5.4%) (odd ratio 1.82 95% confidence intervals 0.51 to 6.45). Paraprotein isotypes were similar in the two groups and the clinical characteristics of the 13 women with paraproteinemia were comparable to an independent population of 10 women with silicone breast implants, CTD and previously diagnosed monoclonal gammopathies. In summary, in this first comprehensive study of serum proteins in women with silicone implants and CTD we found no substantially increased risk of monoclonal gammopathy. Women with silicone implants, however, had unexpectedly low serum globulin and immunoglobulin levels, with or without the subsequent development of CTD. The causes and clinical implications of these findings require further investigation. [unreadable] In another collaborative study, we investigated the clinical significance of immunoglobulin abnormalities in relatives of familial Waldenstrom macroglobulinemia (WM) patients in a follow-up study of three WM families originally evaluated 27 years previously. This study is the longest comprehensive follow-up of WM families to date. Based on the results of serum protein electrophoresis, immunofixation electrophoresis and clinical data, IgM monoclonal gammopathy seemed to be a phenotypic marker of WM susceptibility in some families and may carry a high risk of progression to WM. IgM polyclonal gammopathy may also be important in WM families. These observations require validation in larger studies and, if confirmed, may be used to identify a cohort (relatives with IgM monoclonal gammopathy) for future prevention strategies.